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Fundamentals Part 2 > Pharmacokinetics > Flashcards

Flashcards in Pharmacokinetics Deck (129):
1

What is one example of where only transcellular transport is used? (no paracellular)

capillaries in the blood brain barrier

2

List the equation used to calculate the pH of a weak acid

pH=pKa + log (A-/HA)

3

List the equation for the pH of a weak base

pH=pKa + log(B/BH+)

4

What occurs as pH=pKa

there is an equilibrium between the ionized and unionized forms of weak acids and bases

5

what is the equation for the volume of distribution Vd

Vd=amount of drug/concentration,
Vd=D/Co

6

what is the concept of the pH gradient

weak acids accumulate on more basic side of membrane & vice versa for bases

7

a coupled transport refers to:

a Secondary Active Transport carrier protein which uses an electrochemical potential difference to fuel transport

8

what is "controlled release" "extended release" or "sustained release"

to slow the dissolution, u can slow the absorption, in turn, prolonging the drug in the body system. Allowing for more uniform therapeutic effect while minimizing adverse effects

9

how does prolonging the duration of action effect the onset of action

it delays the onset

10

why would having a controlled/extended or sustained release be a problem

if treating someone was life-threatening where a rapid response is needed, you wouldn't want the delayed onset of action that results from a controlled release

11

dissolution

for a drug to be absorbed it must 1st be dissolved in the fluid

12

how can you alter the rate of dissolution

coating it with wax or other water-soluble material, also complexing it with ion-exchange resins...altering the shape of drug, for example tablets dissolute slow, granules intermediate and fine particles are rapid

13

why is compliance easier for patients when you prolong the duration of action

patients only have to take drug twice a day vs. four, etc. (decreases frequency needed to take it)

14

under normal conditions how long would a drug be expected to stay in the stomach? small intestines? and Colin?

stomach: 2-4 hours, SI:4-10 and colonic tract: 12-50 hours

15

First-Pass Metabolism

when drug administered orally is absorbed into the blood stream and broken down by liver b4 reaching full systemic circulation

16

what types of factors affect bioavailability of a drug

insufficient absorption, decreased absorption, first-pass metabolism and other demographic factors (age, sex, exercise, genetics, stress, GI surgery)

17

what is measured by comparing the Area Under the Curve (AUC) after IV and oral administration to the plasma concentration over time

bioavailability

18

when the maximum (peak) plasma concentration is reached when:

drug elimination rate equals absorption rate

19

when does drug elimination begin

as soon as the drug enters the bloodstream

20

ADME stands for what referring to pharmacokinetics

Administration, Distribution, Metabolism, and Excretion

21

Molecular Weight

smaller passes easier, when females are lactating a larger drug would prevent it from accumulating in the breast milk

22

why are weak acids/bases IDEAL drugs

since they are present in both ionized and unionized forms, they can pass through lipid membranes or through water in body cause they transfer easily btw the two.

23

what is the bioavailability for a drug administered through an IV

100% (higher risk for adverse effects)

24

This type of pathway doesn't require drug to be lipid soluble and no energy is required

paracellular pathway

25

what is the principle driving force for the paracellular pathway

hydrostatic pressure

26

why do we see a saturation point with facilitated diffusion vs. passive

only so many transporter proteins can work at one time...

27

why would it be wrong to give 1/5 the dose of a drug to a neonate based on the fact that they are 1/5 the weight of an adult when referring to body water

babies have more percent of body water than adults (75-80%) vs. adults 60 and elderly ~50%

28

acidic drugs tend to bind to plasma proteins. Describe it's volume of distribution

Low

29

what is the main point to understand about perfusion rates affecting distribution...

more perfusion to the kidneys, lungs, heart, liver, and brain (Phase I) THAN the adipose, muscle, and skin (Phase II)

30

what are the two isoenzymes we should remember and % do they represent in Phase I of oxidation....

3A4 (50%) and 2D6 (30%)

31

What does Phase I of metabolism include

oxidation mainly with CYP450 (3A4) to make drug polar, able to be eliminated

32

Liver Disease=

Dose Adjustment!

33

What is a Loading Dose refer to

doubling dose may lead to a "kick start" or earlier onset of action

34

Define Steady-State

situation where drug in=drug out and plasma levels of drug are steady regardless of when sample is taken.

35

define third spacing and list examples

very little fluid exist in this space & it has no function... pleural cavity & peritoneal cavity, and GI tract

36

how can third-spacing lead to hypovolemia

either pt is hemorrhaging or losing fluids into one of the cavities where its not helping the body

37

What accounts for the decrease in % body water with increasing age

adipose tissue

38

How would you adjust dose for infant with more % body water

increase the dose

39

how would you adjust the dose for an elderly with less % body water

decrease the dose

40

What organs would be considered Phase I of distribution based on CO & Q

heart, lungs, liver, kidneys, and brain

41

what organs are considered Phase II of distribution

muscle, skin, adipose tissue

42

why is the measurement of volume distribution said to be "apparent"

its assumed the concentration of drug found in the sample represents all other compartments in body. Rarely true due to protein binding, ion trapping

43

how is volume of distribution related to drug concentration

Inversely

44

many acidic drugs are highly protein-bound thus would they have a small or large Vd

small

45

what protein are acids most likely to bind to

albumin

46

which type of protein are bases most likely to bind to

alpha-1 glycoprotein
also lipoproteins

47

what is albumin's main funciton

maintain osmotic pressure of blood, transport endogenous substances.

48

this protein tranports plasma lipids & may bind drugs if albumin is saturated

lipoprotein

49

where are erythrocytes made

bone marrow of membranous bones-vertebrae, ribs, sternum

50

hemolytic anemia caused by penicillin is what type of hypersensitivity rxn

Type II, when penicillin binds to RBC, body recognizes as "foreign" launches an IgG attack

51

what would you see in patients with edema

dilute drugs (increase Vd) that are highly water soluble or protein bound

52

in capillaries what is the primary route of transportation of a drug

paracellular,

53

list the relative permeability of capillaries from greatest to least

liver>kidney>muscle=fetus>brain

54

what has a more permeable capillary bed between the muscle and the liver

the liver

55

list the restricted spaces of the body & why fat soluble drugs moe better across these membranes

brain, placenta, and eye; fat soluble move better across these restricted spaces b/c its dependent upon passive diffusion

56

what are examples of protected tissues

blood-brain barrier, placental barrier, and blood-retinal barrier

57

What is ion trapping

weak acidic drugs trapped in basic environments & vice versa

58

drugs dissolve in water (water soluble drugs) accumulate in which spaces as reservoirs

blood & interstitial fluid

59

how are protein-bound drugs reservoirs?

they are inactive when bound and as the same free drug is used up, then they are released

60

what type of reservoir can lead to toxicity

tissue protein bound drugs b/c they prolong action hence leading to harmful accumulations

61

what are examples of toxicity due to tissue protein bound drugs

aminoglycosides (antibiotic class), renal tissue (temporary renal failure), and central auditory tissue (deafness)

62

in the BBB, what cells promote formation & health of the tight junctions making drug penetration dependent on transcellular transport

astrocytes

63

what does inflammation do to the BBB which makes it possible to treat meningities with water soluble antibiotics

breaks down the barrier, increasing permeability

64

1. Results of exposure to a toxic metabolite may include

cellular and tissue necrosis, anemia and blood dyscrasias, carcinogenesis, mutagenesis, teratogenesis and fetal death

65

phase I of drug clearance involves:

oxidation/reduction which doesn't change water solubility, but alters property of the drug...

66

phase ii involves

synthetic rxns, increase polarity & water solubility. increasing drug clearance.. involve conjugation with endogenous substances (glucoronic acid, sulfate, glycine

67

what is the only phase II reaction occurs in the liver

glucuronidation

68

where is glucuronides secreted from?

the bile

69

what are two other substances that conjugate with amino acids in Phase II that are not secreted in bile

glutamine and glycine

70

what is the mechanism for acetaminophen accumulating as a toxic metabolite in the liver

it undergoes phase II preferentially (doesn't require prior phase I oxidation) and if overdosed, overwhelms the phase II- forcing phase I metabolism.

71

rate of metabolism relationship with half life

inverse

72

what are factors affect rate of metabolism

drugs, liver disease, malaria, neoplastic disease (cancer) Age, nutritional status (protein poor-lower metabolism) vs. high protein diet speeds up) smoking & veggies speeds up. Grapefruit juice increases bioavailibiility by inhibiting intestinal elimination. intestinal microflora

73

factors affect glomerular filtration of a drug

MW, diseases,

74

describe enterohepatic recycling or recirculation

drugs with more neutral charges (greater lipid solubility) may be reabsorbed from the intestines & re-enter the liver

75

what pH does the urine range

4.5-8

76

Urine becomes more acidified in what part of the nephron

distal tubules and collecting ducts

77

What could you do to increase the exctretion of weak acids that in a normally acidic urine would be reabsorbed...

give them 1 to 2 mEq/kg sodium bicarbonate (alkanize) every 3-4 hrs

78

How could alkanizing the urine of a patient with a cocaine or aspirin overdose help them excrete them faster?

normally when the urine is acidic, this promotes the reabsorption of weak acids back to the body thus alkanizing the urine would counteract this process.

79

Where does active tubular reabsorption occur? What molecules is this important for? Unimportant?

Proximal tubules, important for endogenous molecules like ions, glucose, amino acids
Minimally important for most drugs

80

Active Tubular Secretion

runs against a concentration gradient, many drugs eliminated this way.

81

How will a drugs half-life be affected if it has a lower affinity for the carrier mediated tubular secretion than another drug with a higher affinity

The half life will be prolonged

82

in general drugs are excreted with bile when they have already undergone:

hepatic metabolism, but some may enter bile unmetabolized

83

drugs & metabolites present in bile are released in the gi tract via:

major duodenal papilla

84

what types of drugs does pulmonary excretion work on

volatile drugs that are unchanged

85

what are two factors affect drug excretion through breast milk

more concentration & less plasma protein binding lead to higher exretion

86

what is meant by the term "dosing to effect"

when condtions are present that alter 1/2 life (liver/renal ds) a physiologic marker for effectiveness or toxicity is often used to adjust dosing.

87

why doesn't half life give you a good picture for full elimination

metabolites may be stored in fat cells so although it only takes 2 hours to reach t1/2, it usually takes 5X to assume total elimination

88

in terms of an efficacy half life, how could a drug produce an effect after its eliminated

acting intracellularly and/or remains partly bound to the receptor or is a "hit & run" that alters receptor.

89

What does the Cyclooxygenase enzyme do

synthesizes prostaglandins from arachidonic acid

90

What role does prostaglandins play

pain, inflammation, cell proliferation, mucus production, fever,

91

Which type of COX enzyme would be termed the "housekeeper"

COX 1, secretes mucus to protect stomach from gastric juices; clots blood, regulates perfusion to kidneys

92

This COX enzyme is referred to aa inducible

COX 2

93

COX 2 plays a role in :

inflammation site: increases prostaglandin production(macrophages & synoviocytes)

94

Why is COX 1 referred to as constitutive i.e. what does constitutive mean?

It is present at all times; and it has the power to form a part of something

95

HOw might a stomach ulcer form?

COX1 inhibitor

96

how can inhibiting COX2 lead to high blood P & increased CV disease risk

they are found lining interior of the bv

97

What role does COX2 play int he kidney, which if inhibited would lead to fluid retention

regulating water & sodium excretion

98

what is acetaminophen's thought MOA

acts primarily in CNS to inhibit COX2 enzymes hence decreasing pain.... indirectly blocks.... direct effects on hypothalamus' heat regulating center accounts for antipyretic nature

99

What is acetaminophens indication & dosing

it is an analgesic & antipyretic; only analgesic approved to use in infants <6 months. Dose-650-1000mg 4-6 hrs/day

100

What organ is most likely toxic from acetaminophen & why?

liver, normally the drug goes through Phase II metabolism here as part of the CYP450, but if it is being all used (overdose) then in can bump into Phase I producing a toxic metabolite that can accumulate in hepatocytes and destroy them.

101

IBuprofin causes the following ADR's

GI (peptic ulcer disease) CV risks (stroke & MI) & kidney (high albumin binding displacing other drugs/blockage of prostaglandins regulate Q)

102

in addition to IBuprofin having antipyretic & analgesic properties similar to acetaminophen, what else does it function to do

anti-inflammatory

103

what is Ibuprofin's MOA

it is non-selective on COX1 and COX2

104

why doesn't acetaminophen have anti-inflammatory effects

Since it works in the CNS, it doesn't inhibit COX in the peripheral tissues

105

What is the onset of acetaminophen

30-60 min

106

which drug would you choose to treat osteoarthritis with? It is less potent, and has less ADR's

acetaminophen

107

Why is acetaminophen not as likely as IBuprofin to cause kidney problems

It's protein binding is only 10-25%

108

What is Ibuprofins affinity to Albumin

90-99% bound

109

What are the 2 most important things we should know about drugs

1. any drug can cause a symptom 2. any drug can cause an allergic rxn

110

What is the dosing for Ibuprofin

200-400 mg every 6 hours

111

Why is using ideal body weight in obese patients wrong for dosing?

we would underdose them because adipose tissue blocks the full effect of drugs getting to tissues

112

when using "adjusted body weight" they use a factor around what percent to give a medication for obese

40% (rather than using the pt weight)

113

Dose using "total body weight" means:

more drug for the patient who weighs more

114

Many carcinogens are only activated after:

biotransformation of a reactive metabolite which may cause toxic effects

115

What are some examples of problems caused by toxic metabolites

teratogenesis, mutagenesis, carcinogens, blood dyscrasias, tissue necrosis

116

How do anaerobic bacteria contribute to reabsorption in liver (enterohepatic recirculation)

they can hydrolyze the conjugated drug

117

The mechanism of extretion through the bile is mainly what type of transport?

carrier mediated active; transporters present in canalicular membrane of the hepatocyte

118

What are some examples of semi-polar solvents

alcohol & ketones (may act to induce a certain degree of polar/nonpolar)

119

What is cosolvency refer to:

a blending of solvents with varying degrees of polarity to create optimal polarity for solute to dissolve in solvent!

120

which form (ionized/unionized) would be favored in a weak acid and weak base at low pH?

HA and HB+

121

Would the pH be low or high when a solution is dominated by A- and HB

high or basic pH

122

What are some examples of tissue reservoirs

bone, GI tract, thyroid

123

How does meningitis make it possible for water-soluble antibiotics to cross the bbb and work to treat it

the inflammation breaks it down, makes membrane more permeable

124

how does ion trapping occur in fetal circulation?

Since the fetal plasma is more acidic than the mother's weak bases accumulate across the placenta

125

What is the underlying cause of diabetic retinopathy

the blood ocular barrier (consists of tight junctions/nonfenestrated capillaries) becomes leaky due to inflammation & leads to eye damage

126

What is responsible for differences in drug metabolism in patients of varying ethnicities

*CYP450 enzyme polymorphism

127

What landmarks begin and end the duodenum

pylorus to suspensory ligament(Treitz ligament)

128

what is the mesentery's main function

supplies blood, nerves, and lymph to the SI and GI

129

HOw does the Crypt of Leiberkuhn contribute to health and maintenance of SI

consist of undifferentiated cells to replace epithelium